Identifying the primary functions of the transcription factor Foxg1 in brain development

Lead Research Organisation: University of Edinburgh
Department Name: Biomedical Sciences


In the embryo, cells in different parts of the brain contain different sets of molecules that control the way that those cells develop and the way that they influence the development of other cells. Several such molecules have been found and one of these, called Foxg1, is the subject of this research. In mutant mice that are unable to make Foxg1, important regions of the brain do not develop normally but we do not understand exactly why this happens. Our aim is to identify the brain cells that need Foxg1 within themselves and why they need it. For example, Foxg1 might be needed to make particular sets of cells multiply at a normal rate, to make immature cells mature properly, to make cells connect correctly with other cells and to make cells send appropriate molecular instructions to other cells. To find out where Foxg1 acts to influence these processes we aim to make animals that are a mixture of mutant cells lacking Foxg1 and normal cells. If cells need Foxg1 within themselves, then mutant cells that do not have Foxg1 should not develop normally even if they are able to interact with cells that do have Foxg1. If a group of cells relies on molecules produced under the control of Foxg1 by another group of cells, then cells in the first group should develop normally (even if they lack Foxg1 themselves) provided they are able to interact with cells that do have Foxg1 and are, therefore, able to produce the important molecules. We plan to make chimaeric mice, containing a mixture of mutant and normal cells, to discover which mutant cells do not develop normally, and in what ways they fail to develop, even when normal cells are present for them to interact with. Defects that persist will indicate processes that require the actions of Foxg1 within the defective cells. In new mutant mice that we plan to make, we shall remove Foxg1 from subsets of the cells that normally express it, to find whether it has primary actions in those subsets and whether it has knock-on effects on other subsets. The results will contribute basic knowledge on the control of early brain development, which is poorly understood. In the long-term this will be relevant for attempts to understand and eventually treat neurological diseases thought to have their origin during early brain development.

Technical Summary

Regionally-expressed transcription factors are crucial for early development of the brain. Foxg1, a transcription factor whose expression is confined mainly to the developing forebrain, is needed for the ventral telencephalon and optic stalk to form, for normal maturation of the dorsal telencephalon and for the guidance of retinal ganglion cell axons. Our aims are to tease apart the primary and secondary actions of Foxg1 by identifying (i) which cell groups require Foxg1 within themselves, i.e. cell-autonomously, (ii) what the cell-autonomous actions of Foxg1 are within those cells and (iii) whether there are cell groups that require the action of Foxg1 in interacting cells. This will be done by generating chimaeric mouse embryos containing a mixture of cells that are wild-type and mutant for Foxg1 and by generating conditional mutants that lack Foxg1 in only some parts of the domain where the factor is normally expressed. In chimaeras, we shall study whether the defects of cells lacking Foxg1 in the ventral telencephalon, dorsal telencephalon and optic stalk observed in mice lacking Foxg1 persist when these cells are mixed with wild-types cells. Defects that persist will indicate processes that require the cell-autonomous actions of Foxg1. Defects that are rescued will indicate processes that require the actions of Foxg1 in interacting cells. We shall generate a new line of mice carrying a floxed Foxg1 allele and cross these mice with strains expressing Cre recombinase in subregions of the Foxg1 expression domain to identify the primary sites of action of Foxg1 in the control of cellular proliferation, differentiation and axonal navigation. We shall use these new mutants to test the hypothesis that Foxg1 is required postnatally for the development of retinotopic projections from retinal ganglion cells to the optic tectum. The results will contribute basic knowledge on the control of early brain development, which is currently poorly understood.


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Magnani D (2010) The Gli3 hypomorphic mutation Pdn causes selective impairment in the growth, patterning, and axon guidance capability of the lateral ganglionic eminence. in The Journal of neuroscience : the official journal of the Society for Neuroscience

Description Wellcome trust Project Grant
Amount £490,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2009 
End 02/2012